In-vivo Efficacy of a Phage Cocktail Therapy that Targets ESBL-producing Klebsiella Urinary Tract Infections Clinical Isolates

Jariah, R. O. A.; Schofield, J.; West, K.; Michniewski, S.; Jameson, E.; Onions, L.; Saravanan, A.; Yesilkaya, H.; Millard, A. D.; Clokie, M. R. J.; Haines, M. E. K.

doi:10.1101/2025.04.01.646603

bioRxiv · 10.1101/2025.04.01.646603

In-vivo Efficacy of a Phage Cocktail Therapy that Targets ESBL-producing Klebsiella Urinary Tract Infections Clinical Isolates

Jariah, R. O. A.·Schofield, J.·West, K.·Michniewski, S.·Jameson, E.·Onions, L.·Saravanan, A.·Yesilkaya, H.·Millard, A. D.·Clokie, M. R. J.·Haines, M. E. K.

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Abstract

Uropathogenic Klebsiella pneumoniae strains, are of major concern of with respect to antimicrobial resistance, which has sparked interest in phage therapy as an alternative, or compliment to antibiotics. However, very limited in vivo data on phage therapy safety and efficacy for treating UTIs is available. To address this, we developed a model to test these parameters for a phage cocktail optimised for Extended Spectrum Beta-Lactamases (ESBL)-producing Klebsiella UTI strains. Female C57BL/6J mice were infected with K. pneumoniae Top52 then received a single dose of the purified therapeutic phages, with observations over seven days. Results showed a significant reduction of bacterial burden in urine, bladder, and kidney samples starting from 4 h post-treatment until Day 7. Phage treatment also reduced local inflammation within the bladder. Additionally, cytokine profile demonstrated an increase in anti-inflammatory IL-10 and a decrease in pro-inflammatory IL-6, indicating a synergy between phage and the host immune response.

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Jariah, R. O. A., Schofield, J., West, K., Michniewski, S., Jameson, E., Onions, L., Saravanan, A., Yesilkaya, H., Millard, A. D., Clokie, M. R. J., Haines, M. E. K.. 2025-04-01. In-vivo Efficacy of a Phage Cocktail Therapy that Targets ESBL-producing Klebsiella Urinary Tract Infections Clinical Isolates. https://doi.org/10.1101/2025.04.01.646603

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